Abemaciclib/ET Combo Improves Responses vs Chemo in Aggressive HR+/HER2– Breast Cancer

Treatment with frontline abemaciclib (Verzenio) combined with endocrine therapy (ET) demonstrated a superior overall response rate (ORR) compared with chemotherapy in patients with hormone receptor–positive/HER2-negative advanced breast cancer with aggressive disease characteristics, according to data the phase 2 ABIGAIL study (NCT04603183) shared at the 2024 ESMO Congress.

The study included 162 patients from 29 sites between June 2021 and January 2024. Patients were randomly assigned 1:1 to arm A (n = 80; 72.5% letrozole) or arm B (n = 82). The primary end point of the study was met in the intent-to-treat population as the 12-week ORR in arm A was 58.8% and 40.2% in arm B (odds ratio, 2.12; 95% CI, 1.13-3.96; P =.0193).

For safety at 12 weeks, the toxicity profile was as expected with each treatment strategy. Patients had better tolerance with the combination including endocrine therapy, except for diarrhea of any-grade (68% with abemaciclib and ET vs 23% with paclitaxel).

“The ABIGAIL trial demonstrated abemaciclib combined with endocrine therapy showed superior efficacy after 12 weeks compared [with] the standard chemotherapy as a frontline treatment strategy for [patients with] hormonal receptor-positive, HER2-negative advanced breast cancer with aggressive disease characteristics,” explained Juan De la Haba Rodriguez, MD, Maimónides Institute of Biomedical Research, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain, during an oral presentation of the data.

Looking at safety, any-grade treatment-emergent adverse events (TEAEs) seen in 10% of patients or more in the abemaciclib plus ET and paclitaxel arms included neutropenia (27% vs 29%), anemia (16% vs 26%), leukopenia (3% vs 11%), asthenia (37% vs 48%), alopecia (5% vs 39%), nausea (25% vs 18%), neurotoxicity (0% vs 28%), constipation (8% vs 14%), decreased appetite (13% vs 9%), and neuropathy peripheral (0% vs 11%). Grade 3 or greater TEAEs seen in both arms consisted of neutropenia (9% vs 1%) and diarrhea (3% vs 1%).

ABIGAIL Trial Overview

While one standard first-line treatment for patients with hormone receptor–positive/HER2-negative advanced breast cancer remains a CDK4/6 inhibitor given with ET, chemotherapy given as induction treatment is often used for patients who are at risk of rapid progression. The ABIGAIL trial sought to challenge chemotherapy induction prior to starting an ET-based therapy approach in this patient population.

The open-label, multicenter, non-inferiority study enrolled adult patients with hormone receptor–positive/HER2-negative advanced breast cancer. Inclusion in the study was open to patients who had received no prior systemic therapy for their advanced breast cancer, those who had measurable disease, an ECOG performance status of 0 or 1, and 1 or more aggressive disease criteria.

Patient characteristics were balanced between arms and the median age of patients included was 58 years (range, 26-85). In the abemaciclib plus ET arm, 65% of patients had an ECOG performance status of 0 compared with 63.4% in the paclitaxel arm. Further, 64% of patients had visceral disease present, 36% had 3 or more metastatic sites, and 36.2% in the abemaciclib plus ET arm and 28.1% in the paclitaxel arm had de novo advanced breast cancer.

In arm A, patients received oral abemaciclib at a dose of 150 mg twice a day in 28-day cycles plus letrozole given orally at a dose of 2.5 mg a day or fulvestrant via intramuscular injection at a dose of 500 mg on days 1, 15, 29, and once monthly thereafter, at investigator criteria. In arm B, intravenous paclitaxel at a dose of 90 mg/m2 was given to patients on days 1, 8, and 15 every 28 days for 12 weeks. This was followed by abemaciclib with ET. The stratification factor was the presence of visceral disease.

In addition to the primary end point of 12-week ORR as per blinded independent central review using RECIST 1.1, a key secondary end point evaluated was safety.

The study is ongoing with investigators continuing to assess the long-term efficacy, as well as other secondary end points like progression-free survival.

Reference

de la Haba-Rodriguez J, Cortés J, Di Cosimo S, et al. ABIGAIL: Randomized phase II study of abemaciclib plus endocrine therapy (ET) with or without a short course of induction paclitaxel in patients (pts) with previously untreated HR-positive/HER2-negative advanced breast cancer (HR+/HER2- ABC) with aggressive disease criteria. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA23.